An investigation of the flexibility and dynamic modes of DNA in solution is proposed. For this purpose, the reactions of various nucleic acids with a series of "oversized" intercalative ligands (and especially water-soluble mesosubstituted porphyrins) will be considered. These molecules will serve as probes of open regions of DNA that may aid in determining the time range and detailed mechanisms of distortions and dislocations within the helix. Correlations of the relative steric requirements of the ligand molecules with their base pair specificities will be pursued. The experimental findings derived from this research might provide a rational basis for drug design and delivery systems relevant to therapies based upon DNA modification. Porphyrins in general and these derivatives in particular are known to accumulate in tumors. A number of cancer therapies are being developed-based upon porphyrin chemistry; it is thus important to characterize the sequence specificity of these compounds in addition to using them to probe helix dynamics.